Collaborative Research: Mechanobiology of a Resilient Bone Extracellular Matrix: A Multiscale Perspective on How Bats Achieve Exceptional Mechanical Properties in their Wing Bones

蝙蝠是唯一能够进行动力飞行的哺乳动物。蝙蝠在哺乳动物中也是不寻常的，因为它们的翼骨在飞行时会弯曲。有些骨骼弯曲到几乎90度，不会骨折。然而，关于构成蝙蝠骨的材料如何允许这种不寻常的弯曲，或者控制这种骨组织的沉积和维持的基因，人们知之甚少。通过研究蝙蝠骨骼与陆地哺乳动物相比的结构和遗传基础，这项工作将展示骨骼细胞是如何共同创造这种不同寻常的骨骼的。通过在培养皿中构建像蝙蝠一样的骨骼基质，有可能获得一种合成材料的生物印迹，这种材料可以像蝙蝠骨骼一样弯曲而不断裂。到目前为止，俄亥俄州东北部已经有超过200名学生参加了为幼儿园前到高中生举办的关于蝙蝠如何长出翅膀的研讨会，这种推广活动将继续下去。此外，世界各地的学生将受益于一个新创建的教育网站。除了这些工作坊，作为该项目的一部分工作的高中、本科生和研究生将接受分子、生物力学和纳米结构生物技术的跨学科培训。通过确定在体内和体外产生弹性细胞外基质所需的机制，这项研究有望扩大我们对骨性能如何通过组成分子过程和微观结构进行调节的理解。我们通过进行结构和生物力学分析(从纳米尺度到整个骨骼)以及体内和体外对游动和非游动哺乳动物肢体骨细胞的分子分析，整合了柔性骨中RNA的表达和力学性能。具体地说，这一结果可能表明哺乳动物的骨细胞如何在2D培养环境中合成蝙蝠样的基质，并最终允许在体内合成专门的3D基质。总体而言，这项研究将允许多个领域的研究理解并利用进化作为制造异常灵活的骨骼所需的关键机制。

Bats are the only mammals capable of powered flight. Bats are also unusual among mammals because their wing bones bend during flight. Some bones bend to almost 90 degrees and do not fracture. However, little is known about how the materials that make up bat bones allow this unusual bending, or the genes that control the deposition and maintenance of this bone tissue. By studying the structure and genetic underpinnings of bat bones compared to terrestrial mammals, this work will show how bone cells work together to create this unusual bone. By building a bat-like bone matrix in a petri dish, it may be possible to get a bioprint of a synthetic material that can bend like bat bones without breaking. Workshops for pre-Kindergarten to high school students about how the bat got its wings have so far reached over 200 students in Northeastern Ohio and this outreach will be continued. Additionally, students around the world will benefit from a newly created educational website. Beyond these workshops, high school, undergraduate, and graduate students working as part of this project will receive interdisciplinary training in molecular, biomechanical, and nanostructural biological techniques. By identifying the mechanisms required to create a resilient extracellular bone matrix in vivo and in vitro, this study is expected to expand our understanding of how bone performance is adjusted by constituent molecular processes and microstructure. We integrate RNA expression and mechanical performance in a flexible bone by undertaking structural and biomechanical analyses (nano-scale to whole bone), as well as in vivo and in vitro molecular assays of limb bone cells of volant and non-volant mammals. Specifically, this result could show how mammalian bone cells can synthesize a bat-like matrix in a 2D culture environment, and eventually allow the synthesis of a specialized 3D matrix in vivo. Overall this study will allow for multiple fields of research to understand and capitalize on what evolution selected as the key mechanisms needed to make an unusually flexible bone.